Expression and targeting of lymphocyte function-associated antigen 1 (LFA-1) on white blood cells for treatment of allergic asthma

Anukriti Gupta, Vanessa Espinosa, Lindsey E. Galusha, Vahid Rahimian, Katie L. Miro, Amariliz Rivera-Medina, Chinnaswamy Kasinathan, Eugenio Capitle, Helen A. Aguila, Scott C. Kachlany

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Allergic asthma is a chronic respiratory disease that results from an exaggerated inflammatory response in the airways. Environment stimuli, such as pollen and HDM, cause activation and migration of inflammatory WBCs into the respiratory tract, where they cause lung damage. Migration of these WBCs is dependent on the active configuration of the β2 integrin LFA-1. The experimental therapeutic agent LtxA specifically targets active LFA-1 and causes cell death. We investigated the association between LFA-1 and allergic asthma and hypothesized that targeting LFA-1 with LtxA could be an attractive strategy for treatment of the condition. We examined LFA-1 (CD11a) levels on PBMCs from patients with allergic asthma compared with healthy controls. Patients exhibited a significantly higher percentage of PBMCs expressing LFA-1 than healthy controls. Furthermore, the level of LFA-1 expression on patient PBMCs was greater than on healthy PBMCs. We identified a unique cellular population in patients that consisted of CD4 CD11ahi cells. We also evaluated LtxA in a HDM extract-induced mouse model for allergic asthma. LtxA caused resolution of disease in mice, as demonstrated by a decrease in BALF WBCs, a reduction in pulmonary inflammation and tissue remodeling, and a decrease in proinflammatory cytokines IL-4, IL-5, IL-9, IL-17F, and IL-23α in lung tissue. LFA-1 may serve as an important marker in allergic asthma, and the elimination of activated WBCs by use of LtxA could be a viable therapeutic strategy for treating patients with this condition.

Original languageEnglish (US)
Pages (from-to)439-446
Number of pages8
JournalJournal of Leukocyte Biology
Volume97
Issue number3
DOIs
StatePublished - Mar 1 2015

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Keywords

  • CD11a
  • House dust mite
  • Inflammation
  • Leukothera
  • Leukotoxin
  • LtxA

Fingerprint Dive into the research topics of 'Expression and targeting of lymphocyte function-associated antigen 1 (LFA-1) on white blood cells for treatment of allergic asthma'. Together they form a unique fingerprint.

Cite this